vasopressin--1-(1-mercaptocyclohexaneacetic-acid)-2-(o--methyl-l-tyrosine)-8-l-arginine- and Angina-Pectoris

We examined the involvement of endogenous vasopressin and platelet-activating factor (PAF) in the pathogenesis of two types of experimental angina in urethane-anaesthetised male Wistar rats. In the first model, epinephrine (10 microg kg(-1)) was injected into the tail vein, followed at the development of the maximum blood pressure response, i.e., 30 s later, by phentolamine (15 mg kg(-1)). In the second model, the vasopressin V1 receptor agonist ornithine-vasopressin (ornipressin; 0.5 IU kg(-1), i.v.) was administered. The heart rate, mean arterial blood pressure and surface electrocardiogram (ECG, standard lead II) were registered simultaneously. As a measure of myocardial ischaemia, at 1 min after phentolamine or ornipressin administration, we found significant ST-segment depression, lasting for more than 10 or 5 min, respectively. Pretreatment (15 min, s.c.) with the vasopressin V1 receptor antagonist Mca1,Tyr(Me)2AVP (the Manning peptide; 0.02-0.2 microg kg(-1)) or the platelet-activating factor receptor antagonist ginkgolide B (BN 52021; 0.25-2.5 mg kg(-1)) alone caused a dose-dependent reduction of the ST-segment depression. Concurrent administration of the two antagonists in their threshold doses (0.02 microg kg(-1) and 0.25 mg kg(-1)) also attenuated the ST-segment depression in both models. Neither antagonist affected the blood pressure or heart rate changes throughout the studies. Our results suggest that endogenous vasopressin and platelet-activating factor interact synergistically in provoking myocardial ischaemia in vivo in experimental angina in the rat.

Topics: Angina Pectoris; Animals; Antidiuretic Hormone Receptor Antagonists; Arginine Vasopressin; Blood Pressure; Diterpenes; Dose-Response Relationship, Drug; Drug Interactions; Electrocardiography; Epinephrine; Ginkgolides; Heart Rate; Hormone Antagonists; Injections, Intravenous; Lactones; Male; Myocardial Ischemia; Ornipressin; Phentolamine; Platelet Activating Factor; Rats; Rats, Wistar; Receptors, Vasopressin; Time Factors; Vasoconstrictor Agents; Vasopressins